Intensive Care Medicine - Annual Update 2009

Table of contens

List of Contributors

Common Abbreviations

I Genomics and Proteomics

Rethinking Sepsis: New Insights from Gene Expression Profiling Studies

Introduction

How to Identify and Measure Heterogeneity

Sources of Heterogeneity in Sepsis Patients

New Insights from Gene-expression Studies

Limitation of Current Risk Stratification Methods

Host Response in Sepsis is More Complex Than Previously Thought

There Is Strong Evidence of Heterogeneity at the Genomic Level

Genomic Heterogeneity

What Gives Rise To Genomic Heterogeneity?

Main Sources of Genomic Variability

Further Questions on an Existing Sepsis Model

Functional Mapping of Sepsis Genome to Monitor Immune Function

Conclusion

References

Mitochondrial Genetics and Sepsis

Introduction

Oxidative Phosphorylation and ATP Generation

Reactive Oxygen Species

Apoptosis

Mitochondria and Sepsis

Mitochondrial Genetics

Mitochondrial Haplogroups

Haplogroups and Human Disease

Haplogroups and Mitochondrial Function

Mitochondrial Biogenesis

Conclusion

References

Lung Proteomics in Intensive Care

Introduction

The Search for Biomarkers

What is a Biomarker?

The Need for Proteomics in the Intensive Care Unit

Genomics versus Proteomics

Lung Proteomics

Basics

What Intensivists Should Know About Proteomic Methods

Caveats

Applications in ALI/ARDS

In vitro

In vivo Animal Models

Clinical Studies

Future Directions

Epithelial Lining Fluid

Exhaled Breath Condensates

Decreasing the Noise to Discover the Signal

Conclusion

References

II Inflammatory Response

The Host Response to Sepsis

Introduction

Epidemiology and Genetic Variability

Pathogen Recognition Systems

Coagulation and Anticoagulation

Immune Suppression and Apoptosis

HMGB1 and RAGE

The Cholinergic Anti-inflammatory Pathway

Macrophage Migration Inhibitory Factor

C5a and C5a Receptor

Conclusion

References

Endotoxin Tolerance: Mechanisms and Clinical Applicability

Introduction

Mechanisms of Endotoxin Tolerance

Toll-like Receptors

Anti-inflammatory Hypothesis and Leukocyte Reprogramming

Endothelial Function and Microcirculation during LPS Tolerance

Clinical Applicability and Therapeutic Possibilities

Cross-tolerance

Conclusions

References

Oxidative Stress and Endothelial Dysfunctionduring Sepsis

Introduction

Sources and Actions of ROS and RNS in the Endothelium during Sepsis

Mechanisms of Endothelial Dysfunction during Sepsis

Conclusion

References

Measurement of Carbon Monoxide: From Benchto Bedside

Introduction

Carbon Monoxide Measurement

Carbon Monoxide Concentrations in Critically Ill Patients

Carbon Monoxide Concentrations and Lung Diseases

Carbon Monoxide Concentrations and Other Diseases

Conclusion

References

Monitoring Immune Dysfunction in Septic Patients: Toward Tailored Immunotherapy

Introduction

Monocyte Dysfunction

Functional Testing

Cell Surface Marker Expression

Mechanisms Responsible for Monocyte Dysfunction

Restoration of Monocyte Functions

T Lymphocyte Dysfunction

Functional Testing

Cell Surface Marker Expression

Mechanism Responsible for Lymphocyte Dysfunction

Restoration of Lymphocyte Functions

Conclusion

References

III Current and Future Management of Sepsis

Source Control in the ICU

Introduction

What is ‘Source Control’?

Elements of Source Control

Drainage

Decompression

Debridement

Restoration of Anatomy and Function

Do we need to perform Source Control?

When to Perform Source Control?

The Role of the Intensivist

What if Source Control is Impossible or Fails?

Special Considerations in Critically Ill Patients

Timing of Source Control

Definitive Therapy or Temporary Measures

How to Recognize Failed Source Control?

Conclusion

References

IgM-enriched Immunoglobulins in Sepsis

Introduction

Mechanisms of Action of IVIG in Sepsis

Differences between IgG- and IgM-enriched Immunoglobulins

Clinical Significance of IgM-enriched IVIG

Conclusion

References

Clarithromycin: A Promising Immunomodulatorin Sepsis

Introduction

Indirect Evidence for an Immunomodulatory effect of Macrolides in Pneumonia

Lessons from Animal Studies

Clinical Efficacy of Clarithromycin as an Immunomodulator in Sepsis

Conclusion

References

High-flow Hemofiltration as an Adjunctive Therapy in Sepsis

Introduction

Mechanism of Action: Hemofiltration as a New Shield against the ‘Chaos Theory’ and ‘Complex Non-linear Systems’ in Sepsis

Recent Animal Trials and Clinical studies Highlighting the Crucial Roles of Dosing and Timing

Practical Aspects for the Bedside Clinician

Future Directions Regarding the Use of Hemofiltration in Sepsis

Conclusion

References

Economic and Social Burden of Severe SepsisE. Silva

Introduction

Concepts

Direct Costs of Sepsis Management

Direct Costs of Sepsis Management in Developing Countries: A Brazilian Experience

Indirect Costs and Burden of Illness

Impact of Therapeutic Strategies on Costs

Conclusion

References

IV Proposed Targets for New Therapies

Lymphocyte Apoptosis in Sepsis and Potential Anti-apoptotic Strategies

Introduction

Mechanisms of Apoptosis

Pathways Involved in Apoptosis

Evidence in Animals

Caspase-cascade

Fas/CD95-induced apoptosis

Mitochondrial Pathway

Evidence in Humans

Therapeutic Molecular Targets

Conclusion and Perspectives

References

The Pivotal Role of Beta-adrenoreceptors in Critical Illness Pathophysiology

Introduction

New Concepts in Adrenoreceptor Signaling Biology

Desensitization of Beta-adrenoreceptors

Catecholamine-induced Immune Dysregulation

Beta-adrenoreceptor-mediated Metabolic Effects of Critical Illness

Beta-adrenoreceptor-mediated Effects on Barrier Gut Function

Specific Beta-adrenoreceptor-mediated Roles in Common Critical IllnessPathophysiology

Traumatic Head Injury

Cardiovascular Dysfunction during Critical Illness

Acute Lung injury

Limitations of Current Experimental/clinical Data

Conclusion

References

Non-septic Acute Lung Injury and Inflammation: Role of TLR4

Introduction

Participation of TLR4 in Ischemia-reperfusion Injury

Heme Activates TLR4 by Different Mechanisms than does LPS

Acute Lung Injury Produced by Avian Influenza Virus H5N1 or Acid Aspiration is Dependent on Activation of TLR4 By Oxidized Phospholipids

Fragmented Hyaluronic Acid activates TLR4

TLR4 Participates in Late Inflammatory Responses in which HMGB1 Plays a Contributory Role

Heat Shock Proteins (HSP) Induce Pro-inflammatory Cytokine Release through TLR4

TLR4 Participates in Ethanol-induced Inflammation

Acetaminophen-induced Liver Injury is TLR4-dependent

Conclusion

References

Hydrogen Sulfide: A Metabolic Modulator and a Protective Agent in Animal Models of Reperfusion Injury

Introduction

The Biological Chemistry of Hydrogen Sulfide

H2S as an Inducer of a State Resembling Suspended Animation

Protective Effects of H2S in Local or Whole-body Ischemia or Ischemia-reperfusion

Conclusion

References

V Septic Shock

‘Myocardial Depression’ or ‘Septic Cardiomyopathy’?

Introduction

Septic Cardiomyopathy: A Secondary Cardiomyopathy in the Scope of the Systemic Disease, ‘Sepsis’

How to Quantify Septic Cardiomyopathy?

Septic Cardiomyopathy is of Prognostic Relevance

Septic Cardiomyopathy: Triggers and Mechanisms

Pump Failure

The Role of Arrhythmias in Septic Cardiomyopathy

The Heart as a ‘Cytokine Producer’

Impaired Regulation of Cardiac Function in Septic Cardiomyopathy

Possible Mechanisms of Impaired Regulation of Cardiac Function in Sepsis: Pacemaker HCN Channels as Targets

Causal Approaches towards the Treatment of Acute Septic Cardiomyopathy

Conclusion

References

Determinants of Tissue PCO2 in Shock and Sepsis: Relationship to the Microcirculation

Introduction

Mechanisms of Increase in Venous and Tissue PCO2: The Basics

Intramucosal Acidosis in Sepsis

Conclusion

References

Refining the Tools for Early Goal-directed Therapy in Septic Shock

Introduction: Initial Management of Septic Shock

Overview of Early Goal-directed Therapy

Therapeutic Steps and Goals and Proposed Refinements

Fluid Titration to Predictors of Fluid Responsiveness

Fluid Titration to Mean Arterial Pressure

Vasopressor Titration to MAP

The Goal: Tissue Perfusion

Red Blood Cell Transfusion

Inotrope Therapy

Other Issues

Early Recognition of Severe Sepsis

Early Antimicrobials

Vasopressor Weaning

Conclusion

References

VI Intravenous Fluids

Hyperchloremic Metabolic Acidosis: More than Just a Simple Dilutional Effect

Introduction

Mechanisms Underpinning pH Regulation: A Physico-chemical Approach

Effects of Plasma Volume Expansion on pH

Clinical Consequences of Hyperchloremic Metabolic Acidosis

Fluid Resuscitation and Electrolyte Manipulation

Pulmonary Compensation/Acute Lung Injury

Coagulation Cascade

Microvascular Flow

Immune Activation or Suppression

Survival

Conclusion

References

Old versus New Starches: What do We Know about their Differences?

Introduction

Hydroxyethyl Starch Pharmacokinetics

Volume Effects

Renal Effects

Coagulation and Bleeding

Tissue Storage

Pruritus

Long-term Survival

Conclusion

References

Impact of Hydroxyethyl Starch on Renal Function

Introduction

Pharmacokinetic Profile of HES Solutions

Pathomechanisms of HES-induced Renal Dysfunction

Clinical Evidence of HES-induced Renal Dysfunction

Conclusion

References

Rational Approach to Fluid Therapy in Acute Diabetic Ketoacidosis

Introduction

Historical Perspective

Pathophysiology

Aims of Fluid Therapy

Optimal Management

Evidence Base for 0.9 % Saline

Problems with 0.9 % Saline

Evidence Base for 0.45 % Saline

Evidence Base for Hartmann’s Solution

Evidence Base for Colloids

Conclusion

References

VII Hemodynamic Support

Cardiac Filling Volumes and Pressures in Assessing Preload Responsiveness during Fluid Challenges

Introduction

Goals and Effects of Fluid Loading: Defining Preload and Fluid Responsiveness

Filling Pressures and Volumes of the Heart

Physiological Considerations and Clinical Implications

Conclusion

References

Update on Preload Indexes: More Volume than Pressure

Introduction

Filling Pressures (CVP and PAOP)

Continuous Right Ventricular End-diastolic Volume (cRVEDV)

Global-end Diastolic Volume and Intrathoracic Blood Volume

Conclusion

References

Monitoring Arterial Blood Pressure and Cardiac Output using Central or Peripheral Arterial Pressure Waveforms

Introduction

Wave Contour in the Central and Peripheral Arteries

Agreement between Central and Peripheral Blood Pressure in Specific Clinical Situations

Influence of the Site of Blood Pressure Measurement on Continuous Cardiac Output Estimation

Conclusion

References

Intrathoracic Pressure Regulation for the Treatment of Hypotension

Introduction

Active Intrathoracic Pressure Regulation Therapy for Apneic Hypotension Patients

Intrathoracic Pressure Regulation Therapy in Cardiac Arrest with CPR

Intrathoracic Pressure Regulation Therapy and CPR

Intrathoracic Pressure Regulation Therapy and Survival Outcomes in Hemorrhagic Shock

Intrathoracic Pressure Regulation Therapy and Sepsis

Potential Adverse Consequences and Limitations of Intrathoracic Pressure Regulation Therapy

Conclusion

References

Functional Hemodynamic Monitoring: A Personal Perspective

Introduction

Use of Dynamic Responses to Identify Nascent Cardiovascular States

Preload Responsiveness

Cardiovascular Sufficiency

Future Trends

References

VIII Airway Management

Endotracheal Intubation in the ICU

Introduction

Care Management Bundle to Increase the Safety of EndotrachealIntubation in the ICU

Pre-intubation Period

Per-intubation Period

Post-intubation Period

Conclusion

References

Pediatric Advanced Airway Management Training for Non-anesthesia Residents

Introduction

Risks associated with Tracheal Intubation and Provider Competence

Non-neonatal Intubation

Neonatal Intubation

Demand for Pediatric Airway Management Competence in Pediatric Resident Trainees

Process of Acquisition and Retention of Pediatric Tracheal Intubation Competence

Acquisition of Intubation Skill Competence

Retention of Intubation Skill Competence

Validation of and Evidence for Simulation in Tracheal Intubation Training

Future Directions

Conclusion

References

Automatic Tube Compensation in the Weaning Process

Introduction

Automatic Tube Compensation

Commercially available Automatic Tube Compensation Systems

Potential Clinical Uses of Automatic Tube Compensation

Increasing the Predictive Potential of a Spontaneous Breathing Trial

Studies using commercially available ATC systems

Potential Disadvantage of Reducing Imposed Workload

Use of Automatic Tube Compensation as a Weaning Predictor

Practical Aspects of using Automatic Tube Compensation

Conclusion

References

IX Mechanical Ventilation

Extracorporeal Membrane Oxygenation for Cardiac and Pulmonary Indications: Improving Patient Safety

Introduction

Application of ECMO Today

Indications for ECMO

Components of ECMO Devices

Further Development of ECMO

Oxygenator

Blood Pump

Modifications of ECMO Console and Circuit

Pumpless Extracorporeal Lung Assist

Control and Safety

Automation for Related Applications

Available Control and Safety Concepts for ECMO

New Control and Safety Concepts

Conclusion

References

Patient-ventilator Interaction during Non-invasive Ventilation

Introduction

NIV in Acute Respiratory Failure

Triggering of the Ventilator

Pressurization Slope

Level of Pressure Support

Cycling

Masks

Conclusion

References

Variable Mechanical Ventilation: Breaking the Monotony

Introduction

Patterns of Variability and their Characterization

Rationale for the Use of Variable Patterns in Mechanical Ventilation

History of Variable Mechanical Ventilation

Variable Controlled Mechanical Ventilation

Variable Assisted Mechanical Ventilation

Why does Respiratory Function Improve during Variable Mechanical Ventilation?

Is Variable Mechanical Ventilation Equivalent to Regular Ventilation with Intermittent Sighs?

Can Variable Mechanical Ventilation be Injurious?

Limitations of Variable Mechanical Ventilation

Conclusion

References

Life-threatening Asthma: Focus on Lung Protection

Introduction

Epidemiology

Definitions

Risk Factors

Pathophysiology of the Acute Asthma Attack

Therapeutic Approach

Pharmacological Therapy

Non-Invasive Ventilation

Intubation

Mechanical Ventilation

Assessing Lung Inflation

Analgesia, Sedation, Paralysis, and Inhaled Anesthetics

Heliox

Rescue Therapies

Conclusion

References

X Respiratory Monitoring

Bedside Monitoring of Diaphragm Electrical Activity during Mechanical Ventilation

Introduction and Background

Bedside Monitoring of EAdi

Conclusion

References

Electrical Impedance Tomography

Introduction

How Electrical Impedance Tomography Works

Reconstruction Algorithms

Patterns of Applying the Electrical Current

Absolute versus Difference Images

Spatial and Temporal Resolution

Clinical Applications

Assessment of Lung Recruitment and Lung Collapse

Detection of Pneumothorax and Pleural Effusion

Correct Placement of Endotracheal Tube

Potential Future Applications of Clinical Relevance

Conclusion

References

Regional Ventilation Delay Index: Detection of Tidal Recruitment using Electrical Impedance Tomography

Introduction

Individual PEEP Setting is Essential

Global and Regional Lung Function Parameters

Elecrical Impedance Tomography

The Concept of the Regional Ventilation Delay Index

Implementing Regional Ventilation Delay Index in Clinical Practice

Conclusion

References

Different Approaches to the Analysis of Volumetric Capnography

Introduction

Capnography: Types and Applications

Invasive Volumetric Capnography Variables

Non-invasive Volumetric Capnography Variables

Techniques for Volumetric Capnography Analysis

A New Algorithm for Volumetric Capnography Analysis

Conclusion

References

Variation in Extravascular Lung Water in ALI/ARDS Patients using Open Lung Strategy

Introduction

Measurement of EVLW at the Bedside

EVLW in ALI/ARDS Patients

Ventilation Strategy in ALI/ARDS and EVLW Variations

Conclusion

References

Clinical Utility of Extravascular Lung Water Measurements

Introduction

Measurement of EVLW

Gravimetry

Transpulmonary Dilution Techniques

Double indicator dilution technique

Single indicator dilution technique

Limitations of the Measurement of EVLW by Transpulmonary Dilution Techniques

Underestimation of EVLW during ARDS

Effects of Positive End-expiratory Pressure (PEEP)

Other limitations

Clinical Utility of EVLW

Diagnosis of Pulmonary Edema

Identification of the Mechanism of Pulmonary Edema

Prognostic Evaluation of Patients with ALI/ARDS

Guidance of Fluid Therapy in ARDS

EVLW for Guiding Ventilatory Strategy

Conclusion

References

Rationalizing the Use of Surgical Critical Care: The Role of Cardiopulmonary Exercise Testing

Introduction

Why Use Cardiopulmonary Exercise Testing as an Assessment Tool?

Which Patients should Undergo Cardiopulmonary Exercise Testing?

Cardiopulmonary Exercise Testing in Practice

1. Preparation

2. Data collection

3. Unloaded Cycling

4. Ramping Phase

5. Recovery Phase

Interpretation of Cardiopulmonary Exercise Test Data

1. The Anaerobic Threshold

2. Ischemic Heart Disease

a) The oxygen pulse response (VO2/heart rate)

b) Relationship of VO2 to work rate

c) Ventilatory Equivalent for CO2 (VE/VCO2)

Risk Stratification and Management using Cardiopulmonary Exercise Testing

Case Reports

Conclusion

References

Advanced Minimally Invasive Hemodynamic Monitoring of the High-risk Major Surgery Patient

Introduction

Definition and Role of Perioperative Optimization

Preoperative Period

Intraoperative Period

Postoperative Period

Overview of Some Current Advanced Hemodynamic Monitors

Non- or Minimally-invasive Measurement of Cardiac Output

Comparison of cardiac outputs from monitors used contemporaneously in the operating room

Use of the LiDCOplus and LiDCOrapid in the management of intraoperative hypotension

Decline in Use of Central Venous Catheterization for Major Surgery

Conclusion

References

Post-pneumonectomy Pulmonary Edema

Introduction

Diagnostic Criteria

Prevalence

Pathology

Etiology

Inflammation

1. Eicosanoids

2. Vascular endothelial growth factor (VEGF)

3. Tumor necrosis factor (TNF)- and the interleukins (IL)

Fluid Therapy and Reduction in Volume of the Pulmonary Vascular Bed

Disrupted Lymphatic Drainage

Oxidative Damage and Ischemia-Reperfusion Injury

Ventilation

Comorbidities

Chest Drains

Transfusion of Blood Products

Conclusion

References

The Role of Phenylephrine in Perioperative Medicine

Introduction

Pharmacological Characteristics of Phenylephrine

Contraindications for the Use of Phenylephrine

Use of Phenylephrine to Treat Perioperative Arterial Hypotension

General and Regional Anesthesia

Cardiac Surgery

Non-cardiac Vascular Surgery

Cesarean Section

Use of Phenylephrine in Postoperative Intensive Care Medicine

Vasodilatory Shock after Cardiac Surgery and Cardiopulmonary Bypass

Use of Phenylephrine in Sepsis-related Arterial Hypotension

Use of Phenylephrine in Cardiopulmonary Resuscitation

Summary and Conclusion

References

Role of the Calcium Sensitizer, Levosimendan, in Perioperative Intensive Care Medicine

Introduction

Mode of Action

Dosage and Pharmacokinetics

Clinically Relevant Side Effects

Metabolism

Severe Sepsis and Septic Shock

Perioperative Administration

Right Ventricular Dysfunction

Cardiogenic Shock

Cardiopulmonary Resuscitation

Conclusion

References

Inhaled Nitric Oxide Therapy in Adult Cardiac Surgery

Introduction

Generation and Metabolism

Local Cardiopulmonary Effects

Non-cardiovascular Effects

Pulmonary Hypertension and Right Ventricular Failure after CardiacSurgery

Pulmonary Hypertension

Right Ventricular Failure

Diagnosis

Administration of Nitric Oxide

Cardiac Surgery

Valve Operations

Adult Congenital Heart Disease

Ventricular Assist Device

Heart Transplantation

Lung Transplantation

Trial Data Relating to Outcome

Conclusion

References

XII Cardiac Function

Use of Natriuretic Peptides in the EmergencyDepartment and the ICU

Introduction

Natriuretic Peptides are Quantitative Markers of Cardiac Stressand Heart Failure

Clinical Indications: Patients with Acute Dyspnea

Diagnostic Value of Natriuretic Peptides in Patients with Acute Dyspnea

Prognostic Value of Natriuretic Peptides in Patients with Acute Dyspnea

Impact of Natriuretic Peptide on the Management of Patients with Acute Dyspnea

Added Value of Using Natriuretic Peptide in the Management of Patients with Acute Dyspnea

ICU Perspective

Conclusion

References

Abnormalities of the ST Segment

Introduction

Electrocardiographic Evaluation

Electrocardiographic Differential Diagnosis – ST Segment Abnormalities

Acute Coronary Syndrome

Benign Early Repolarization

Acute Myopericarditis

Left Ventricular Aneurysm

Other Patterns with ST Segment Abnormality

References

Functional Mitral Regurgitation in the Critically Ill

Introduction

Definition

Pathophysiology

Diagnosis

Therapeutic Management

Medical

Surgical

Conclusion

References

XIII Cardiopulmonary Resuscitation

Feedback to Improve the Quality of CPR

Introduction

The Importance of Quality CPR

Chest Compressions

Interruptions in Chest Compressions

Ventilation Rate and Hyperventilation

The Quality of CPR is often Sub-optimal during Clinical Resuscitation Attempts

Strategies for Improving the Quality of CPR

Real-time Feedback during CPR Training and Actual Resuscitation

Post-event Debriefing

Future Developments in Technology

Conclusion

References

The Post-cardiac Arrest Syndrome

Introduction

Phases of the Post-cardiac Arrest Syndrome

Pathophysiology of Post-cardiac Arrest Syndrome

Post-cardiac Arrest Brain Injury

Post-cardiac Arrest Myocardial Dysfunction

Systemic Ischemia/reperfusion Response

Persistent Precipitating Pathology

Treatment of the Post-cardiac Arrest Syndrome

Airway and Ventilation

Circulation

Disability (optimizing neurological recovery)

Post-cardiac Arrest Prognostication

Organ Donation

Conclusion

References

Use of a Standardized Treatment Protocol for Post-cardiac Resuscitation Care

Introduction

Chain of Survival

The Post-resuscitation Syndrome

Early Coronary Intervention

Induced Mild Hypothermia

Cerebral Blood Flow and Mean Arterial Blood Pressure

Hemodynamic Support and Monitoring

Ventilation

Blood Glucose and Electrolyte Monitoring

Thrombolytic Therapy Aimed at Improving Brain Perfusion

Brain Monitoring

Prevention of Infection

Use of Sedation, Analgesia and Paralyzing Agents

Slow, Passive or Active Re-warming and the Prevention of Fever

Prognostication

Future Perspectives

Conclusion

References

Therapeutic Hypothermia after Cardiac Arrest

Introduction

Effects of Hypothermia on Neurological Function Following Cardiac Arrest

Effects of Hypothermia on Myocardial Function after Cardiac Arrest

Timing and Methods for Inducing Hypothermia

Preliminary Experience with Selective Brain Cooling: Effects on Neurological and Myocardial Functions

Conclusion

References

XIV Renal Function

Biomarkers of Acute Kidney Injury in Critical Illness

Introduction

Conventionally used Indices of Renal Injury

Biomarkers of Renal Injury

Serum Markers

Urine Markers of AKI

Data on Biomarkers of AKI in Critical Illness

Biomarkers on the Horizon

What should an Intensivist do When Faced with an Abnormal Biomarker Result?

Conclusion

References

The Role of Biomarkers in Cardiac Surgery- associated Acute Kidney Injury

Introduction

What are the Characteristics of an Ideal Biomarker of Cardiac Surgery-associated-AKI?

Diagnostic Performance: How Good is a Test?

What Biomarkers are Needed?

What Biomarkers are Currently Available and How Good are They?

What Biomarkers are Under Development?

Neutrophil Gelatinase-associated Lipocalin

Interleukin-18

Kidney Injury Molecule-1

Cystatin C

Limitations of New Biomarkers

How will New Biomarkers Change the Diagnosis and Treatment of AKI?

Conclusion

References

Neutrophil Gelatinase-associated Lipocalin: An Emerging Biomarker for Angina Renalis

Introduction

Discovery of NGAL as an AKI Biomarker

NGAL for the Early Diagnosis of AKI

NGAL for Monitoring the Response to AKI Therapy

NGAL for the Prediction of AKI Outcomes

Limitations of NGAL as an AKI Biomarker

Conclusion

References

XV Hepatosplanchnic Function

ICG Clearance Monitoring in ICU Patients

Introduction

Physiology of Indocyanine Green

Principles of Measurement

Invasive Methods

Non-Invasive Methods

Limits of ICG Pharmacokinetics Interpretation

The Current Place of ICG in Clinical Practice (Table 2)

Prognostic Marker in the Intensive Care Unit

Hepatosplanchnic Hemodynamics In Different Clinical Settings

Cirrhosis

Major Hepatic Surgery

Liver Transplantation

Conclusion

References

Acute-on-Chronic Liver Failure in Cirrhosis: Defining and Managing Organ Dysfunction

Introduction

Defining Acute-on-Chronic Liver Failure

Quantifying Organ Dysfunction in Cirrhosis

Pathogenesis

Associated Organ Dysfunction

Adrenal

Brain

Blood (Coagulopathy)

Cardiovascular

Gut/nutrition

Immune System

Muscle/metabolic

Portal Hypertension/variceal Bleeding

Renal

Respiratory

Conclusion

References

How does Intra-abdominal Pressure Affect the Daily Management of My Patients?

Introduction

Definitions

Epidemiology and Etiology

Techniques for IAP Measurement

Transvesical IAP Measurement

Transgastric IAP Measurement

Recommendations for IAP Measurement

Should I Measure IAP in all Patients?

What Technique should I Use?

What Frequency?

When Should I Stop IAP Measurement?

The Impact of IAH on Organ Function Management

Effect on Cardiovascular Management

Effects of IAH on Respiratory Management

The Effect of IAH on Renal Function Management

The Effect of IAH on the Management of the Patient with Intracranial Hypertension

The Influence of IAH on the Management of Specific Patient Groups

IAH and Patients with Severe Sepsis

IAH and the Burn Patient

IAH and the Hematology Patient

IAH in Morbidly Obese Patients

A New Concept: Acute Bowel Injury and Acute Intestinal Distress Syndrome

Conclusion

References

XVI Nutrition

The Curse of Overfeeding and the Blight of Underfeeding

Introduction

Energy Requirements in the Critically Ill

Is it Better to Underfeed?

Underfeeding is also a problem

Parenteral versus Enteral Nutrition

Why then should there be a Link between Nutritional Excess and Infection?

Tight Glycemic Control and Nutrition Delivery are Linked

Conclusion

References

Enteral Feeding during Circulatory Failure: Myths and Reality

Introduction

Splanchnic Consequences of Feeding and of Circulatory Failure

Nutritional Status of the Cardiac Patient

Energy Target and Substrate Requirements

Enteral Feeding Route

Enteral Access

Timing: Preoperative, Early or Conventional Feeding

Enteral, Intravenous, or Combined Nutrition?

Patient Monitoring

Conclusion

References

Enteral Nutrition with Anti-inflammatory Lipidsin ALI/ARDS

Introduction

EPA and GLA Mechanisms of Action

From Bench to Bedside: Using EPA and GLA to Modulate Inflammation

Is the Evidence Enough to Change Practice?

Conclusion

References

Glutamine Supplementation in ICU Patients

Introduction

Background

Metabolic Tolerance

Intravenous Glutamine Supplementation during Continuous Renal Replacement Therapy

Glutamate Concentration and Exchange across the Brain in Head Trauma Patients

Endogenous Glutamine Rate of Appearance

General Comments

Conclusion

References

XVII Glucose Control

Burn Causes Prolonged Insulin Resistance and Hyperglycemia

Introduction

Metabolic Changes following Severe Burn Injury

Attenuation of the Hypermetabolic Response and Associated Hyperglycemia Post-burn

Molecular Mechanisms underlying Insulin Resistance Post-burn

Conclusion

References

Glucose Variability in Critically Ill Patients

Introduction

Glucose Elevation versus Variability

Defining Glucose Variability

Contributors to Glucose Variability

Evidence of Harm in Critically Ill Patients

Future Directions

Conclusion

References

XVIII Adrenal Function

Corticosteroid Biology in Critical Illness:Modulatory Mechanisms and Clinical Implications

Introduction

Activation of the HPA Axis

Transport of Cortisol in the Serum by Cortisol Binding Globulin

CBG and Biochemical Testing of the HPA-Axis

Cellular Activation and Inactivation of Cortisol by 11 HSD-1 and -2

The Glucocorticoid Receptor

Effects of Glucocorticoid Receptor Ligation

Importance of Steroid Responsiveness in the Etiology of Sepsis and SIRS

Conclusion

References

Corticosteroid Treatment of Patients in Septic Shock

Introduction

High-dose Steroid Studies

Low-dose Steroid Studies

The Corticus Study

Adverse Effects of Steroids

The Ongoing Controversy

Mechanism of Corticosteroid Action in Reversing Shock

Recommendations

Conclusion

References

XIX Coagulation

New Anticoagulants: Anti-IIa or Anti-Xa Agents?

Introduction

Factor Xa Inhibitors

Injectable Indirect Factor Xa Inhibitors

Oral Direct Factor Xa Inhibitors

Oral Inhibitors of Activated Thrombin (Factor IIa)

Conclusion

References

Emergency Reversal of Anticoagulants

Introduction

Heparin and Low Molecular Weight Heparin (LMWH)

Pentasaccharides

Vitamin K Antagonists

New Anticoagulants

Aspirin

Thienopyridine Derivatives and Other Antiplatelet Agents

Conclusion

References

XX Neurological Aspects

Monitoring and Managing Raised Intracranial Pressure after Traumatic Brain Injury

Introduction

ICP Monitoring

Techniques

Indications

Variations in Practice

Treatment of Intracranial Hypertension

Sedation and Analgesia

Hyperventilation

Hyperosmolar Therapy

Moderate Hypothermia

Barbiturates

Neurosurgical Interventions

Controversies

What is the Target ICP?

Does ICP Monitoring and Management Improve Outcome?

Complications of Treatment

Multimodal Monitoring

Conclusion

References

Sepsis-associated Encephalopathy

Introduction: Incidence and Diagnosis

Pathophysiology

Brain Signaling in Sepsis

Alteration of Neurotransmission

Mitochondrial Dysfunction, Oxidative Stress and Apoptosis

Endothelial Activation and Blood-brain Barrier Breakdown

Experimental Therapeutic Approach

Conclusion

References

The Role of Imaging in Acute Brain Injury

Introduction

Brain Imaging Modalities

Structural Imaging

Hemodynamic and Metabolic Imaging

Functional Brain Imaging

Applications of Imaging in Acute Brain Injury (Table 1)

Traumatic Brain Injury

Aneurysmal Subarachnoid Hemorrhage

Anoxic-ischemic Encephalopathy

Hepatic Encephalopathy

Sepsis-associated Encephalopathy

Outcome Prediction

Traumatic Brain Injury

Anoxic-ischemic Encephalopathy

Conclusion

References

XXI Malignancies

Acute Tumor Lysis Syndrome: Diagnosis and Management

Introduction

Pathophysiology

Diagnosis, Classification, and Risk Factors

Treatment

Fluid Expansion

Urine Alkalinization

Hypouricemic Agents

Prevention of Nephrocalcinosis

Indication and Timing of Renal Replacement Therapy

Management of Cancer Chemotherapy in Patients with Tumor Lysis Syndrome

Future Research

Conclusion

References

Life-threatening Neurological Complications in Patients with Malignancies

Introduction

Direct Involvement of the Nervous System by the Malignancy

Infiltration of the Brain Parenchyma

Cerebral and Epidural Metastases

Carcinomatous Meningitis

Tumors of the Peripheral Nervous System

Indirect Involvement of the Nervous System by the Malignancy

Autologous and Allogeneic Bone Marrow Transplant Recipients

Infections

Cerebrovascular Disease

Neurological Paraneoplastic Syndromes

Iatrogenic Events

Metabolic Complications

Diagnostic Strategy in Cancer Patients with New Neurological Manifestations

Conclusion

References

Should We Admit Critically Ill Cancer Patients to the ICU?

Introduction

Outcome in Critically Ill Cancer Patients Requiring Advanced Life Supporting Therapy

Reasons for Improvement in Outcomes and the Role of Non-invasive Ventilation

Prognostic Indicators: Subgroups with a Better and Worse Outcome

Triage Decisions in an Individual Patient and the Importance of Good Communication

Conclusion

References

XXII Drug Dosing

Optimizing Drug Dosing in the ICU

Introduction

Pharmacokinetic and Pharmacodynamic Alterations in Critically Ill Patients

Pharmacokinetic Alterations

Alterations in Excretion

Pharmacodynamic Alterations

Pharmacokinetic and Pharmacodynamic Modeling

Back to Basics

Bayesian Forecasting

Population Pharmacokinetics/pharmacodynamics

Application to Critically Ill Patients

Conclusion

References

Relevant CYP450-mediated Drug Interactionsin the ICU

Introduction

The Role of CYP450 in Drug Metabolism

Inhibition and Induction

Interindividual Variability in CYP450-mediated Metabolism

Relevant CYP450-mediated Interactions in the ICU

Drug Interactions Involving CYP3A4

Drug Interactions involving CYP2C9 and CYP2C19: Phenytoin and Warfarin

Drug Interactions Involving CYP2D6

Future Perspectives

Conclusion

References

XXIII Sedation and Analgesia

Sedation and Pain Management in the ICU

Introduction

The Need for Sedation or Analgesia in the ICU

Management of Pain

Anxiolysis

Delirium

Choice of Agent

Monitoring of Sedation

Cognitive Function Evaluation

Physiological and Brain Functional Monitors

Classes of Sedative Agents

Narcotics (Opioids)

Benzodiazepines

Alpha2 Agonists

Neuroleptics/‘antipsychotics’

Propofol

Conclusion

References

The Role of Dexmedetomidine in Intensive Care

Introduction

Mechanism of Action

Pharmacokinetics

General Pharmacodynamics

Cardiorespiratory Effects

Respiratory Effects

Central Nervous System Effects

Gastrointestinal and Other Effects

Interactions

Dosage and Duration of Administration

Sedative and Analgesia Profile

Post-surgical Patients

Medical Patients

Respiratory Profile

Non-sedative Use in the ICU

Safety Profile/adverse Events

Conclusion

References

Monitoring Delirium in the ICU

Introduction

Burden of Illness

Concept

Occurrence Rate

Risk Factors

Cost and Consequences

Screening

Available Tools

Conditions for Screening Programs

Interventions

Prevention and Therapy

Implication for Research and Policy Information

Conclusion

References

XXIV ICU Management

Intensive Care for the Elderly: Current and Future Concerns

Introduction

Current Provision of Intensive Care

Definition of Elderly

Current Age Distribution of Intensive Care Patients

Caring for the Elderly

Triage Decisions

Co-morbidities

Mechanical Ventilation for Elderly Patients

Life after Intensive Care

Caregiver Burden

End-of-life Decisions

Future of Intensive Care for the Elderly

Conclusion

References

ICU Performance: Managing with Balanced Scorecards

Introduction

What is ICU Performance?

Outcomes

Patient Safety

Cost and Resource Utilization

Workforce Performance

Leadership Performance

The ICU environment

What is the Balanced Scorecard

Balanced Scorecards in Healthcare Organizations

Balanced Scorecard Application in the ICU

ICU Workforce Learning and Growth Perspective

ICU Internal Process and Operation Efficiency Perspective

ICU Patient Perspective

ICU Resource Utilization Perspective

ICU Financial Perspective

Successful Implementation of an ICU Balanced Scorecard System

Conclusion

References

XXV End-of-Life Issues

Towards a Neuro-scientific Explanation of Near-death Experiences?

Introduction

Near-death Experiences

Definition

Theoretical Approaches: Spiritual, Psychological and Organic Hypotheses

Clinical Studies

Out-of-body Experiences

Definition

Neuroanatomical Correlates

Conclusion

References

Managing Conflict at the End-of-Life

Introduction

Strategies to Prevent Conflict at the End-Of-Life

Community Awareness and Advance Directives

Futility

Strategies to Avoid Conflict in Acute Hospitals Before Admission to the ICU

Communication

Clinical Practice Guidelines for End-of-Life Care and Decision Making

Cultural, Religious and Racial Aspects around End-of-Life Conflicts

Direct Interventions Dealing with Conflict at the End-of-Life

Striving For Consensus

The Role of Ethical Guidelines in Conflict Resolution

Mediation

The Legal System

Conclusion

References

Strengths and Weaknesses of Substitute Decision Making in the ICU

Introduction

Strengths for the Patient (Table 1)

Substitute Decision-Making Is a Substitute for the Paternalism Model

Substitute Decision-Making is a Substitute for Advance Directives

Substitute Decision-making is the Wish of ICU Patients

Substitute Decision-making is a Real-time Decisional Process

Weaknesses for the Patient (Table 1)

The Designation of a Substitute Decision-maker is Problematic

Substitute Decision-making is not Appropriate for all Patients

Strengths for the Surrogate (Table 1)

Substitute Decision-making is the Wish of the Family

Weaknesses for the Surrogate (Table 1)

Substitute Decision-making is Dependent on Information

The Substitute Decision-maker is not always Objective

The Substitute Decision-maker can lack Capacity

Strengths for the Medical Team (Table 1)

Substitute Decision-making is the Wish of ICU Staff Members

Substitute Decision-making Requires Communication with the Family

Weaknesses for the Medical Team (Table 1)

The Substitute Decision-maker Requires an Assessment of Capacity

Substitute Decision-making is an Interpretation also for Physicians

Strengths for the Community (Table 1)

Weaknesses for the Community (Table 1)

Conclusion

References

Subject Index